CD95 ligand (CD95L, also known as FasL) belongs to the TNF (Tumor Necrosis Factor) family and is the ligand for the “death receptor” CD95 (Fas/APO1). CD95L is a transmembrane “cytokine” whose extracellular domain can be cleaved by metalloproteases, to produce a soluble ligand. This soluble form was initially described as an inert ligand that competes with its membrane-bound counterpart for binding to CD95, thus acting as an antagonist of the death signal. More recent findings have shown that metalloprotease-cleaved-CD95L (cl-CD95L) can actively participate in aggravating inflammation in chronic inflammatory disorders, such as systemic lupus erythematosus (and may exert pro-oncogenic functions by promoting the survival of ovarian and liver cancers and chemotherapy resistance of lung cancers). Binding of transmembrane CD95L to CD95 leads to the recruitment of the adaptor protein Fas-associated death domain protein (FADD) to the intracellular region of CD95 called the death domain (DD). In turn, FADD binds to caspases 8 and 10. This CD95/FADD/caspase complex is known as the Death-Inducing Signaling Complex (DISC) and plays a pivotal role in the initiation of the apoptotic signal. By contrast, cl-CD95L fails to induce DISC formation and instead promotes the formation of an atypical receptosome that we have designated Motility-Inducing Signaling Complex (MISC) (Tauzin S, Chaigne-Delalande B, Selva E, Khadra N, Daburon S, Contin-Bordes C, et al. The naturally processed CD95L elicits a c-yes/calcium/PI3K-driven cell migration pathway. PLoS Biol. 2011; 9:e1001090.). Accordingly, a compound able to reduce the reducing CD95-meditated cell motility is highly desirable.